Dyslipidemia (Lecture 5) Flashcards
The most common clinical manifestation of lipid disorders is atherosclerotic cardiovascular disease (ASCVD) resulting from elevated levels of
apo B-100 lipoproteins
Severe hypertriglyceridemia is primarily associated with an increased risk of
pancreatitis.
The rate-limiting step in cholesterol synthesis is the reduction to mevalonate by 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase, the target of
statins.
LDL is removed from the blood predominantly by the LDL receptor. LDL receptor expression is regulated by ______. Inhibition or decreased levels of _____ thus permit greater LDL receptor circulation and enhanced LDL particle removal from the circulation.
proprotein convertase subtilisin/kexin type 9 (PCSK9)
Apo B lipoproteins, as measured by total, ____ and non-HDL-C levels, predict ASCVD risk in all ages, genders, races/ethnicities, and regions.
LDL-C
All patients with a first LDL-C of ___ mg/dL or higher or triglycerides of 500 mg/dL or higher should be evaluated for secondary causes of hyperlipidemia
160
The LDL-C lowering agents ____ and PCSK9 monoclonal antibodies have been shown to further reduce car- diovascular events when added to background statin therapy in very-high- risk patient populations.
ezetimibe
4 statin benefit groups…
1. Clinical ASCVD
- LDL-C higher than 190 mg/dL
- _____
- ____
- Individuals 40-75 years of age with diabetes with LDL-C 70-189 mg/dL
- Individuals 40 to 75 years of age with LDL-C 70-189
mg/dL AND an estimated 10-year ASCVD risk of >7.5%
In patients with heart failure with reduced ejection fraction attributable to ischemic heart disease who have a reasonable life expectancy and are not already on a statin because of ASCVD, clinicians may consider initiation of ____-intensity statin therapy to reduce the occurrence of ASCVD events.
moderate
High intensity statins?
Atorvastatin 40-80
Rosuvastatin 20
Low-intensity statins?
Pravastatin 10-20
Lovastatin 20
The most straightforward approach in patients with mild to moderate symptoms is to stop the statin, wait until symptoms resolve, and rechallenge with the same statin at a lower dose or another statin at least once a week, depending on the patient’s preferences after being informed of statin benefits (heart attack, stroke, and death reduction). If symptoms do not resolve within ___, the statin is not the cause
2 months
Symptomatic creatine kinase elevations more than 10 times the upper limit of normal, elevated creatinine levels, and myoglobinuria are indicative of ____. The statin should be stopped and the patient should be admitted to the hospital for hydration, close observation, and evaluation for other causes of severe muscle damage.
rhabdomyolysis
Statins have no hepatotoxic effects. If transaminases are ___ times the upper limit of normal, then alanine aminotransferase can be retested in 3 months as reassurance of continued statin safety.
2-3
Two PCSK9 monoclonal antibodies, alirocumab and evolocumab, and ____ have been shown to futher reduce ASCVD risk when added to background statin therapy in high risk ASCVD patients.
ezetimibe
____ is contraindicated for use with statin therapy due to a greater than 30-fold increased risk of myopathy.
Gemfibrozil
Ezetimibe acts in the small intestine to block cholesterol uptake by the Niemann- Pick C1-Like 1 receptor. The resulting lower level of intrahepatic cholesterol stimulates synthesis of ___
LDL-C receptors
Early plaque growth typically involves a compensatory outward remodeling of the arterial wall that preserves the diameter of the lumen and permits plaque accumulation without limitation of blood flow, hence producing no ischemic symptoms. Lesions at this stage can thus evade detection by ___
angiography
Atherosclerotic plaques do not distribute homogeneously throughout the vasculature. They usually develop first in the dorsal aspect of the ____ and proximal coronary arteries, followed by the popliteal arteries, descending thoracic aorta, internal carotid arteries, and renal arteries.
abdominal aorta
Ejection clicks are high-pitched sounds that occur at the moment of maximal opening of the aortic or pulmonary valves. … Ejection clicks may also be called ejection sounds. The ____ correlate of the ejection click is the opening snap, which occurs at maximal opening of a flexibly stenotic mitral or tricuspid valve.
diastolic
The metabolic syndrome (also known as the “insulin resistance syndrome”) refers to a cluster of risk factors, including hypertension, hypertriglyceridemia, ____,___, and visceral obesity
reduced HDL, hyperglycemia
__ has shown the greatest promise as a marker of low-grade systemic inflammation associated with atherosclerotic disease.
CRP
Although it serves as a marker of risk not captured by traditional algorithms, CRP itself does not mediate atherogenesis.
Beta lipoprotein aka?
LDL
The most common clinical manifestation of lipid disorders is atherosclerotic cardiovascular disease (ASCVD) resulting from elevated level of
apo B-100 lipoproteins.
Triglcycerides are not known to be a risk factor for CVD!
____ inhibit the rate-limiting step in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA reductase) which bind acetyl CoA to free cholesterol to create cholesterol esters.
Statins
When do we start monitoring LDL? What about BP?
LDL monitoring starting between 9-11 y/o (maybe earlier if at risk)
BP between 5-6 y/o
You can use an ___ to get a Calcium score
EBCT
You shouldn’t mix fibrates and statins…
check
USPTF/AHAH recommend screening at least once every 5 years for all people over age ___
ACC/AHA recommend calculating the ASCVD risk every ___ for those 40-75 y/o w/o ASCVD or DM w/ LDL at 70-189 mg/dL
20
4-6 years
Many things predispose individuals to statin adverse effects, like?
Unexplained ALT elevations > 3x normal
all the others makes sense
Remember to establish a baseline of muscle symptoms before starting on statins
You hope to avoid the unnecessary discontinuation of statins
However, w/ SEVERE muscle sxs, d/c the statins and work up for possible rhabdo (CK, creatinine, UA for myoglobinuria)
Mild, moderate muscle pains on statin?
D/c statin and Assess for other conditions..
When sxs resolve, start SAME statin (maybe a lower dose) and then monitor for the symptom-drug relationship
If sxs arise again, d/c original statin, let sxs resolve and start a low-dose if different statin
After ___ months of no statin treatment, muscle symptoms or CK
levels do not resolve search for secondary cause
• Should symptoms be found to be unrelated to statin therapy, or if
predisposing condition treated, RESUME statin therapy at the
original dose
2
- Individuals with clinical ASCVD
- Individuals with primary elevations of LDL-C ≥ 190
mg/dL - Individuals 40-75 years of age with diabetes with LDL-
C 70-189 mg/dL - Individuals 40 to 75 years of age with LDL-C 70-189
mg/dL AND an estimated 10-year ASCVD risk of >7.5%
4 statin benefit groups
ASCVD includes?
CHD, stroke, and peripheral artery dz (think this when have diminished pulses)
Remember those > 75 y/o only get moderate intensity statin
k
Unexplained ALT> 3x?
No statin
High intensity statin therapy reduces LDL by how much?
50%
remember, even if patient has positive response, reinforce adherence at 3,12 mos
LDL>190?
HIGH INTENSITY STATIN
Atorvastatin 40-80
Rosuvastatin 20
Benefit group 1… Individuals with ASCVD… when wouldn’t you give HIGH INTENSITY STATIN?
(these individuals normally get HIGH INTENSITY STATINs, so when wouldn’t they?)
Older than 75…
other CI, like ALT>3x
Patients w/ DM, aged 40-75, can either get a moderate or high intensity statin? How do we decide?
If their 10-year ASCVD risk > 7.5 they get high intensity statin
Atorvastatin 40-80
Rosuvastatin 20
Otherwise, go moderate intensity
Group number 4… those with a risk > 7.5, aged 40-75… they can get either mod or high…
Discuss with patient
When triglcyerides are > 500, we can consider fenofibrate and gemfibrozil… However this doesn’t take precedence over statin therapy…
Remember you can’t combine these with statins
Remember even TAG of 499 doesn;’t get treated
Bile acid-binding agents, such as cholestyramine, colestipol, and colesevelam, have adverse effects, most notably?
constipation and bloating
Niacin can cause flushing but we can ___ to mitigate thst
aspirin
Metabolic syndrome is a cluster of at least 3 of the 5…
Obesity Triglycerides HDL (less than 40 for men, less than 50 for women) BP Fasting glucose
More limited data are available from cardiovascular outcomes trials
in highly selected populations for other lipid-modifying agents. The
LDL-C lowering agents ___ and ___ have been shown to further reduce
cardiovascular events when added to background statin therapy in
very-high-risk patient populations.
ezetimibe A7 and PCSK9 mabs
The relative reduction in ASCVD risk from all of these drugs is
proportional to the magnitude of the LDL-C or non-HDL-C lowering.
There are two PCSK9 inhibitors available in the U.S.: ___ and ____
FDA has approved alirocumab for adult patients:
To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease.
As an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-cholesterol FDA has approved evolocumab for adult patients:
To reduce the risk of myocardial infarction, stroke, and coronary revascularization in adults with established cardiovascular disease.
As an adjunct to diet, alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe), for treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-cholesterol
As an adjunct to diet and other LDL-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with homozygous familial hypercholesterolemia who require additional lowering of LDL-C.[1]
alirocumab and evolocumab.
No trials have evaluated bile acid sequestrants added to background
statin therapy. _____ is contraindicated for use with statin
therapy due to a greater than 30-fold increased risk of myopathy.
Gemfibrozil
